Continuous combined hormone replacement therapy with oral 17β-estradiol and norethisterone acetate improves homocysteine metabolism in postmenopausal women

OBJECTIVETo evaluate the effect of a continuous combined oral hormone replacement therapy (HRT) on basal and post-methionine load homocysteine levels in postmenopausal women. DESIGNTwenty-two postmenopausal women (PMW) were randomly allocated to receive either continuous combined oral HRT (2 mg of estradiol plus 1 mg of norethisterone acetate;n = 11) or no treatment (controls, n = 11) for 6 months. A methionine oral load (0.1 g/kg body weight) was performed in each subject at time 0 and after 6 months. Serum homocysteine levels were measured by high-performance liquid chromatography in samples collected at time 0 and at 4, 8, and 24 h after the methionine load, while levels of vitamin B6 (by high-performance liquid chromatography) and B12 and folate (both by ELISA) were assayed in samples collected at time 0. RESULTSSerum levels of glucose and body mass index increased in treated PMW, whereas folate decreased in controls. In treated PMW, basal homocysteine tended to decrease (10.6 ± 3.3 μmol/L vs. 9.62 ± 2.8 μmol/L, p = 0.062), whereas in controls it significantly increased (10.7 ± 2.65 μmol/L vs. 12.17 ± 3.89 μmol/L, p < 0.05). This increase was not significant after correction for vitamin status (p = 0.072). Homocysteine values 4 h (31.9 ± 13.53 μmol/L vs. 39.83 ± 22.53 μmol/L, p < 0.05) and 8 h (35.1 ± 13.13 vs. 43.34 ± 22.15 μmol/L) after methionine, and integrated homocysteine response to methionine (392.5 ± 133.8 μmol/24 h vs. 458.8 ± 104.8 μmol/24 h;p < 0.05), were significantly reduced in HRT-treated, but not in untreated, PMW. CONCLUSIONSContinuous combined oral HRT with17β-estradiol plus norethisterone acetate reduces homocysteine levels, mainly after a methionine load. This effect seems to be independent of vitamin status and may have positive implications for the prevention of cardiovascular diseases in PMW.